Combination therapies are often used to treat various diseases and conditions. Administering the combination to the patient in a single formulation is more convenient and improves patient compliance. However, administering two pharmaceutically active agents in a single dose is problematic if one of the agents is metabolized more rapidly than the second. Because the dosing regimen will be determined by the agent that is cleared more slowly, the pharmaceutical effect of the more rapidly cleared agent will be absent for a period of time after it is cleared until it is time to re-administer the combination.
This problem could be addressed if the single formulation contains a controlled release composition that comprises the more rapidly metabolizing agent. However, the second more rapidly clearing agent may adversely effect the release profile of the controlled release composition of the first agent. For example, this can occur in liquid formulations when the two pharmaceutically active agents are charged moieties of opposite charge.
Advil Cold and Sinus™ is one example. This combination product contains the decongestant pseudoephedrine and ibuprofen in a syrup. Pseudoephedrine is far more rapidly hydrolyzed than ibuprofen. Although controlled release formulations of pseudoephedrine can be prepared, their release profile is often altered in the presence of ibuprofen.
Therefore, improved pharmaceutical formulations for combination therapies are needed.